Sensory processing and the expression of both simple and complex behaviors depend on rapid communication between disparate parts of the nervous system. This is accomplished by electrically excitable cells that encode and transmit information via electrical signals. Electrical excitability reflects the activity of voltage-gated ion channels that open in response to changes in voltage, allowing the flow of ions across the cell membrane. The properties of excitability depend on the gating behavior, number, type and spatial distribution of these channels in the membrane. changes in these properties have been implicated in modifications of excitability observed during development, following disease or injury to a nerve. A detailed knowledge of the function and regulation of ion channels at the molecular level is prerequisite to understanding the control electrical excitability in developing or pathological systems. This will require the application of electrophysiological, genetic, and molecular biological techniques to the study of voltage-gated ion channels. A powerful system in which all of these approaches can be used is Drosophila. In this proposal focus on sodium and calcium channels Drosophila neurons and myotubes and characterization of genes important in their expression through physiological analysis of mutants. I have identified three genes, para, sei, and tip-E, which alter the macroscopic sodium currents in embryonic neurons. My physiological experiments suggest that para codes for a functional sodium channel protein, consistent with its sequence similarity to a vertebrate sodium channel gene. Although sei and tip-E may also code for sodium channels, they may instead be genes which regulate other aspects of excitability such as number or distribution of channels. Further analysis of mutations at these and additional loci found to affect sodium channels, both at the whole-cell and single channel level will be important in understanding the role of these genes in sodium channel expression. In addition to sodium, calcium ions are important charge carrier in excitable cells. I therefore propose to examine calcium channels in wildtype neurons and myotubes. Genes involved in expression of calcium channels will be identified using a deficiency screen that we have developed to detect chromosomal deletions that alter the expression of whole-cell calcium currents. The results of these studies will define and characterize the molecules important in the function and regulation of ion channels involved in electrical excitability.